AB0007 ASSOCIATION OF rs172378 VARIANT IN C1q GENE CLUSTER WITH SOME CLINICAL AND IMMUNOLOGICAL ASPECTS OF SYSTEMIC LUPUS ERYTHEMATOSUS IN BULGARIAN PATIENTS
Authors: M. Kosturkova, T. Shivacheva, G. Mihaylova, V. Vasilev, M. Radanova
Journal: Annals of the Rheumatic Diseases (2022)

Background Single nucleotide polymorphisms (SNPs) in complement C1q component are found to be linked with systemic lupus erythematosus (SLE), but less is known about their association with the clinical and immunological aspects of the disease. Objectives The aim of the study was to examine five SNPs – rs665691, rs682658, rs172378, rs294179, rs292001 in C1q gene cluster for association with some clinical (age at disease onset, organ involvement, BILAG score, SLICC/ACR DI) and immunological (ANA, anti-dsDNA, complement factors C3 and C4) aspects of SLE. Methods 53 SLE patients were enrolled in this cross-sectional study and relevant clinical information was collected. SNP genotyping was performed on extracted DNAs from patients using a TaqMan allelic discrimination assay. ANA, anti-dsDNA and complement proteins C3 and C4 were measured by IIF, ELISA and radial immunodiffusion resp. Results G-allele and GG-genotype of rs172378 were overrepresented among patients with LN compared to the other SLE patients – 64% vs 31% for G-allele and 48% vs 7.7% and were associated with renal involvement – OR=3.96 (95%CI: 1.53 – 10.23), р=0.005 for G-allele and OR=10.86 (95%CI: 1.29 – 91.58), р=0.028 for GG-genotype. G-allele and GG-genotype were also associated with increased levels of anti-dsDNA antibodies – OR=2.95 (95%CI: 1.21 – 7.18), p=0.017 and OR=6.33 (95%CI: 1.41 – 28.39), р=0.016, resp. G-allele showed weak correlation with earlier age at disease onset (point biserial r=-0.22, p=0.03) and patients, carrying it (GG- and AG-genotypes) were younger at disease onset then those with AA-genotype (p=0.05 and p=0.02 resp.). Conclusion rs172378 associates with some clinical and immunological parameters of SLE, traditionally linked to disease severity, therefore it may possibly play a role in disease pathogenesis. References [1]Guo J, G. Y. (2018). Investigation of C1-complex regions reveals new C1Q variants associated with protection from systemic lupus erythematosus, and affect its transcript abundance. Sci Rep., 8048. doi:10.1038/s41598-018-26380-x [2]Martens HA, Z. M. (2009). Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity. Ann Rheum Dis. 2009 May;68(5):715-20. doi:, 715-20. [3]Mosaad YM, H. A.-R. (2015). C1q rs292001 polymorphism and C1q antibodies in juvenile lupus and their relation to lupus nephritis. Clin Exp Immunol., 23-34. doi:10.1111/cei.12666 [4]Namjou B, K. M. (2012). Identification of novel coding mutation in C1qA gene in an African-American pedigree with lupus and C1q deficiency. Lupus., 1113-8. doi:10.1177/0961203312443993 [5]Petry F, L. M. (2005). Common silent mutations in all types of hereditary complement C1q deficiencies. Immunogenetics, 566-71. [6]Racila DM, S. C. (2003). Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of C1q in patients with subacute cutaneous lupus erythematosus. Lupus, 124-32. [7]Radanova M, V. V. (2015, Mar). Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients. Lupus, 280-9. doi:10.1177/0961203314555173 [8]Rafiq S, F. T. (2010, Aug). Assessing association of common variation in the C1Q gene cluster with systemic lupus erythematosus. Clin Exp Immunol., 284-9. doi:10.1111/j.1365-2249.2010.04185.x Disclosure of Interests None declared